The Indonesian Biomedical Journal

1-15

Authors: Anna Meiliana, Nurrani Mustika Dewi, Andi Wijaya

BACKGROUND: Low back pain (LBP) mostly caused by disc degeneration, reflects to a tremendous of health care system and economy. More knowledge about these underlying pathologies will improve the opportunities that may represent critical therapeutic targets. CONTENT: Basic research is advancing the understanding of the pathogenesis and management of LBP at the molecular and genetic levels. Cytokines such as matrix metalloproteinases, phospholipase A2, nitric oxide, and tumor necrosis factor-α are thought to contribute to the development of LBP. Mesenchymal stem cells (MSCs) transplant to cartilage-like cells and secrete extracellular matrix and encourage nucleus pulposus (NP) cell activity inhibiting NP cell apoptosis, together with some chemical mediators such as cytokines and growth factors become a safe and effective new strategy for intervertebral disc degeneration (IDD) treatment and regeneration. SUMMARY: IDD occurs where there is a loss of homeostatic balance with a predominantly catabolic metabolic profile. A basic understanding of the molecular changes occurring in the degenerating disc is important for practicing clinicians to help them to inform patients to alter lifestyle choices, identify beneficial or harmful supplements, or offer new biologic, genetic, or stem cell therapies.

35-9

Authors: Ferry Sandra

BACKGROUND: Generally ameloblastoma is a locally aggressive, slow growing, non-metastatic epithelial odontogenic benign tumor. However, rarely some ameloblastoma can metastasize in spite of a benign histologic appearance. Targeting ameloblastoma by inducing it into apoptosis could be a beneficial strategy, since many ameloblastoma cases were reported recurrent after surgical therapy. CONTENT: To investigate ameloblastoma in cellular aspect,cytological pattern of ameloblastoma was divided intoouter layer/peripheral and inner layer/central cells. Tumor necrosis factor (TNF)-α, Fas ligand (FasL), TNF receptor (TNFR)1/death receptor (DR)1, TNFR2/DR2, DR4, DR5andFas were highly expressed in central than peripheral cells. Despite inducing apoptosis, TNF-α can induce PI3K leading to Akt and p44/42 mitogen-activated protein kinases (MAPK) activation in AM-1 cells, which later induce cell survival and proliferation. Therefore apoptotic induction in ameloblastoma should be suggested in higher TNF-α concentration. Expression of FasL and Fas are closely associated with squamous metaplasia and granular transformation of the tumor cells, suggesting that apoptosis induced by FasL may play a role in the terminally differentiated or degenerative ameloblastoma cells. TNF-related apoptosis-inducing ligand (TRAIL) has emerged as an apoptotic inducing anticancer agent in tumor cells specifically. TRAIL induced activation of caspases, lowering mitochondrial membrane potential, high number of apoptotic cells in ameloblastoma cells. Therefore, TRAIL could be a potential agent for targeting ameloblastoma, although further study should be explored. SUMMARY: Targeting ameloblastoma by inducing it into apoptosis could be achieved effectively, although some criteria should be considered. Therefore understanding the underlying apoptosis signaling pathways are necessary for inducing ameloblasotma into apoptosis. Investigations on other apoptosis-related molecules, potential apoptosis-inducing natural products, and novel approach in reprogramming, are important in the future for a better anagement of ameloblastoma.

46-50

Authors: Hartanto Bayuaji, Heda Melinda Nazaruddin Nataprawira, Herri Suhari Sastramihardja

BACKGROUND: Polycystic ovary syndrome (PCOS), a common reproductive endocrinologic disorder in woman, was considered to be related to sleep disturbance. This study is aimed to analyze the correlation between excess androgen markers and Athens Insomnia Scale (AIS) in PCOS. METHODS: This observational, cross-sectional study of PCOS was conducted to 31 subjects to evaluate the correlation between serum total testosterone, sex hormone binding globulin (SHBG) and free androgen index with the incidence of sleep disturbance using AIS. Sleep disturbance was present if the score ≥6. The correlation between excess androgen markers and sleep disturbance was analyzed using Pearson’s coefficient of correlation or Spearman’s rho test. Correlation coefficient more than 0.5 with p<0.05 was considered significant. RESULTS: Out of 31 PCOS subjects aged 20-40 years, 39% subjects had AIS score ≥6. Mean serum testosterone in AIS score >6 group was higher than AIS score <6 group but not statistically significant (46.68 vs. 28.49 ng/mL, p>0.05). No significant correlation was found between serum total testosterone, SHBG and free androgen index with AIS score. After adjusting for AIS score, there was the moderate positive correlation between serum total testosterone level although not statistically significant (r=0.54, p=0.07). CONCLUSION: The serum total testosterone level might influence the occurrence of sleep disturbance in PCOS.

56-61

Authors: Edhyana Sahiratmadja, Simeon Penggoam, Ani Melani Maskoen, Alvinsyah Adhityo Pramono, Dias Aryani, Nurul Setia Rahayu, Ramdan Panigoro

BACKGROUND: N-acetyltransferase-2 (NAT2) enzyme, encoded by NAT2 gene, plays a key role in metabolism of anti-tuberculosis (TB) drug isoniazid. Polymorphisms in NAT2 gene may result in different responses to TB therapy. Since TB prevalence in the eastern part of Indonesia is high, the aim of this study is to explore the distribution of NAT2 gene polymorphisms among population from Kupang, Nusa Tenggara Timur. METHODS: A total of 234 respondents were included from Kupang in 2012. Polymorphisms of NAT2 gene were examined using mass screening platform and the genotypes distribution were presented in percentage. To confirm NAT2 gene polymorphisms, polymerase chain reaction (PCR)-sequencing was performed in a subset of population. RESULTS: The polymorphisms of NAT2 gene showed that the distribution of rs1801279 for GG genotype was 100%; whereas the genotype distribution of rs1799930 for GG, GA and AA was 57%, 35.1% and 7.9%, respectively. In a subset of individuals (n13), acetylator status was well determined by PCR-sequencing, resulting in individual with wild type fast acetylator (NAT2*4; n4), intermediate (NAT2*4/*5 or NAT2*4/*6 or NAT2*4/*7; n7) and poor acetylators (NAT2*6/*6 or NAT2*7/*7; n2). CONCLUSION: The amino acid change in rs1799930 result in intermediate and poor acetylator status in Kupang population. This may lead to suboptimal response of TB therapy. Assessing acetylator status before TB therapy is important and may serve as personalized INH therapy.

66-73

Authors: Dwi Ramadhani, Siti Nurhayati, Tur Rahardjo, Mukh Syaifudin

BACKGROUND: Mamuju area in West Sulawesi considered as the high natural background radiation area in Indonesia. Our previous study showed that the mean mitotic index (MI) and nuclear division index (NDI) in lymphocytes of Botteng Village, Mamuju inhabitants was lower compared to control samples. To validate our previous study results, here in this study the evaluation of cell proliferation markers which were MI and NDI in peripheral blood lymphocytes (PBL) of Takandeang Village inhabitants was conducted. METHODS: A total 60 people were enrolled in this study, consisted of 35 samples from Takandeang Sub-Village and 25 from normal background radiation area. MI was calculated manually and automatically using Metafer 3.11.2 imaging system. The NDI defined as proportion of mononucleated, binucleated, trinucleated and tetranucleated cells were conducted using cytokinesis block micronucleus (CBMN) assay. RESULTS: The results of this study showed that the mean manual MI in Takandeang Sub-Village inhabitants was lower compared to control group (4.96±2.25 vs. 5.93±2.14). In contrast, the mean automatic MI (20.37±10.49 vs. 18.87±7.49) and NDI (1.555±0.174 vs. 1.523±0.112) in Takandeang Sub-Village inhabitants was higher compared to the control group. Statistical analysis revealed that the difference of mean manual MI, automatic MI and NDI in Takandeang Sub-Village inhabitants was not significantly different compared to the control group (p>0.05). CONCLUSION: It can be concluded that based on this study the chronic low radiation dose exposure in Takandeang Sub-Village, Mamuju has no significant effect on the lymphocytes proliferation.

79-83

Authors: Hartono Apriliasta Purba, Santi Syafril, Dharma Lindarto

BACKGROUND: Inflammation is one of the factors that associated with insulin resistance which causes type 2 diabetes mellitus (T2DM). Inflammation can be measured by using high sensitivity C-reactive protein (hs-CRP), a quantitative measurement of CRP concentration. Puguntano is a plant that traditionally used for antidiabetic treatment found in North Sumatera. The objective of this study is to know the effect of Puguntano extract on hs-CRP level in newly diagnosed T2DM patient. METHODS: The study was a randomized controlled clinical trial on 24 newly diagnosed T2DM patients. Subjects were divided into 2 groups. The first group was given Puguntano extract with starting doses at 100 mg daily, then the dose was increased in titration up to a maximum dose of 2x100 mg daily depending on blood sugar level monitoring. Meanwhile, the other group (which serves as a control group) was given metformin with starting doses at 500 mg daily, then the dose was increased in titration up to a maximum dose of 3x500 mg per day depending on blood sugar level monitoring. The hs-CRP and HbA1c are assessed at the baseline and after 12 weeks of treatment. RESULTS: The hs-CRP level was decreased in Puguntano group by 1.41 (-7.54-0.52) (p=0.06) and decrease by 0.58 (-7.86-33.41) (p=0.695) in metformin group. There was no difference in hs-CRP level between the two groups (p=0.630). CONCLUSION: Puguntano extract showed the effect of lowering HbA1C and hs-CRP level in T2DM patients, although it was not statistically significant.